Paip1 predicts poor prognosis and promotes tumor progression through AKT/GSK-3β pathway in lung adenocarcinoma

Hum Pathol. 2019 Apr:86:233-242. doi: 10.1016/j.humpath.2018.11.017. Epub 2018 Nov 26.

Abstract

The expression and biological function of Paip1 remain poorly understood in most human cancers. The objective of this research is to investigate its clinical significance and roles in lung adenocarcinoma (LADC). Immunohistochemistry was used to determine Paip1 expression in 58 cases of LADC patients with strict follow-up and 60 cases of adjacent normal lung tissues. Paip1 protein was upregulated in 77.6% (45/58) LADC tissues compared with adjacent normal lung tissues. The overexpression of Paip1 was significantly correlated with histologic grade, clinical stage, and poor prognosis. Small interfering RNA-mediated transfection was performed in A549 and H1299 cells. Paip1 depletion attenuated the proliferation and migration of A549 and H1299 cells. Paip1 also changed the expression of epithelial-to-mesenchymal transition markers including E-cadherin, Vimentin, Slug, and Snail. Furthermore, Paip1 regulated AKT/GSK-3β oncogenic signaling pathways. In conclusions, Paip1 expression is frequently upregulated in LADC, and its overexpression correlates with poor prognosis in LADC patients. Attenuated Paip1 expression suppresses proliferation and epithelial-to-mesenchymal transition-related migration of A549 and H1299 cells by regulating the AKT/GSK-3β signaling pathway.

Keywords: Lung adenocarcinoma; Migration; Polyadenylate-binding protein-interacting protein 1; Prognosis; Proliferation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenocarcinoma of Lung / metabolism*
  • Adenocarcinoma of Lung / mortality
  • Adenocarcinoma of Lung / pathology
  • Aged
  • Cadherins / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Disease Progression
  • Female
  • Glycogen Synthase Kinase 3 beta / metabolism*
  • Humans
  • Lung Neoplasms / metabolism*
  • Lung Neoplasms / mortality
  • Lung Neoplasms / pathology
  • Male
  • Middle Aged
  • Neoplasm Grading
  • Peptide Initiation Factors / metabolism*
  • Prognosis
  • Proto-Oncogene Proteins c-akt / metabolism*
  • RNA-Binding Proteins / metabolism*
  • Signal Transduction / physiology*
  • Snail Family Transcription Factors / metabolism
  • Survival Rate
  • Vimentin / metabolism

Substances

  • Cadherins
  • PAIP1 protein, human
  • Peptide Initiation Factors
  • RNA-Binding Proteins
  • SNAI1 protein, human
  • Snail Family Transcription Factors
  • Vimentin
  • Glycogen Synthase Kinase 3 beta
  • Proto-Oncogene Proteins c-akt